Cure Research Roundup

amfAR-funded researchers present important findings at the 2014 Conference on Retroviruses and Opportunistic Infections

Published Thursday, March 13, 2014

At the recently concluded annual Conference on Retroviruses and Opportunistic Infections in Boston, March 3–6, several scientists reported new findings resulting from research supported by amfAR.

No sign of virus in infant infected at birth
Dr. Deborah Persaud of Johns Hopkins Children’s Center reported that a baby diagnosed with HIV appears to be free of the virus after being put on antiretroviral therapy shortly after it was born. The baby, born outside of Los Angeles, is now nine months old. The mother had advanced AIDS, and had not been taking drugs that would have prevented transmission of the virus to the child. Four hours after the infant was born, doctors administered a three-drug cocktail at a high dose usually used for treatment instead of prevention. The virus began to disappear six days after birth, and was undetectable within 11 days. It is important to note, however, that it is not known whether the baby is “cured” of HIV because she is still on antiretroviral therapy. The first baby cured of HIV, known as the Mississippi child, stopped receiving antiretroviral treatment two years ago and is still HIV-free at the age of 41 months.

Boston patients followed up
Dr. Timothy Henrich of Harvard University and Brigham and Women’s Hospital in Boston continues to follow a pair of patients who had appeared to be free of HIV following stem cell transplants administered to treat lymphoma. After a period of months—longer than any other such cases recorded to date—both experienced a resurgence of virus. Looking for any signs that could have predicted viral rebound, Dr. Henrich examined blood samples taken from both patients immediately before the virus reemerged. He was unable to find any indicators of this kind.

Acute infection and early treatment
In an effort to identify research subjects in the first couple of weeks of infection, Dr. Hiroyu Hatano of the University of California, San Francisco, and colleagues are targeting participants in ongoing studies of PrEP (pre-exposure prophylaxis). Dr. Hatano reported on the case of one patient who initially tested negative for HIV and was put on PrEP in the form of the two-drug combination, Truvada. Tested again one week later, the man was found to be HIV positive after all. The standard test was negative because he had just become infected and had not yet seroconverted (i.e., HIV antibodies did not have time to develop in his blood). The patient was immediately put on antiretroviral therapy, remains on treatment, and after six months has no detectable HIV according to intensive laboratory tests.

T cells and viral reservoirs
Dr. Mathias Lichterfeld of Massachusetts General Hospital, Boston, reported on his progress in characterizing a recently identified subset of T cells. These stem cell memory T cells, or TSCM cells, have properties similar to stem cells and have been identified as particularly important reservoirs of latent HIV. Comparing them to other types of T cells, Dr. Lichterfeld found that TSCM cells have higher concentrations of HIV, suggesting that they could be an important site of viral persistence as well as a source of virus that re-emerges when ART is stopped.

“Shocking” HIV out of its hiding places
Working in the lab of amfAR grantee Dr. Robert Siliciano at Johns Hopkins University, Dr. Greg Laird is looking at drugs that could be used to “shock” HIV out of latent reservoirs so that it can be “killed” by antiretroviral treatment or by the immune system. With a new assay he developed, Dr. Laird tested eight candidate drugs and found that none of them worked particularly well on its own. Finding that the drug bryostatin was the most effective of them, he tested it in combination with each of the others. All combinations worked equally well with the exception of the drug disulfiram—despite having shown early promise as a potential “shock” candidate.

Targeting specific regions of HIV
Also working in the Siliciano lab at Johns Hopkins, Dr. Kai Deng is looking at strategies for eliminating HIV once it can be coaxed out of reservoirs of persistent virus. Viruses that become established in reservoirs are predominantly those that mutated and evaded the immune system, and thus the immune system may have difficulty killing them if they are “shocked” out of cells. Dr. Deng found that cytotoxic T lymphocytes that target the viral protein Gag—in both its mutated and unmutated forms—can improve clearance of the virus.